Clinical Trials
Regulatory & Standards

Enabling Patient Access to Personalised Cell Therapies Through Innovative Technologies

2 September 2020

Dr Ohad Karnieli talks to us about point-of-care manufacturing challenges, solid tumour treatments and taking inspiration from… Mcdonald’s

What are the main challenges that need to be overcome to enable personalised cell therapy point-of-care manufacturing?

The essence of personalised cell therapy is providing tailored cell therapy to meet the patient’s specific illness and needs. This concept takes the challenge of autologous manufacturing to the next level. Not only enabling autologous manufacturing with its labour-intensive processes and donor to donor variation, we now add the tailor-made process. This means that the manufacturing site now has to adjust the process per patient. This kind of tailoring requires changes in process steps, duration, dosage, materials and even quality assurance. Such personalised manufacturing requires highly skilled operators with deep understanding in processes and cells, flexible manufacturing settings and space. These challenges restrict the scalability and availability of the therapies and increases dramatically the already expensive therapies. Therefore, there is a need for an automated, flexible, programable device with metabolic sensing, machine learning and artificial intelligence capabilities designed for minimally skilled operators.

Our industry’s aim is realising a future where autologous advanced therapies, including treatments for solid tumours, are available to patients globally, when and where they’re needed. How close are we to reaching this new healthcare paradigm?

Cancer in general and solid tumours are the second cause of death worldwide. Autologous CAR-T therapies had shown unprecedented clinical efficacy and are regarded as the fifth pillar of treatment, leading the scientific community and industry to further develop solutions. To date, there are several hundred clinical trials using cell-based therapies for the treatment of solid tumours some of which showing promising data. Therefore, in scientific and clinical means, we are getting very close. The biggest gap is the manufacturing of such therapies, without dramatically simplifying the process, the therapies, even if proven very effective, will not reach the needed scale.

There is a need for an innovative new manufacturing platform to simplify the manufacturing and enable a disruptive model of point of care manufacturing. Once such technology enables simple, cost-effective and smart manufacturing, the solid tumour cell therapies can become true cures. Therefore, changing the health paradigm is closer than ever and it depends on smart engineering which will result in an enabling manufacturing platform for point of care such as the ADVA X3 device.

How prepared are we for manufacturing the next generation of autologous cell and gene therapies that are based on TILs, MILs, TCRs, CARs etc?

The short answer is that we are not prepared. We have cutting edge science but in terms of process or scalability, we are back in the early 20th century. It really looks like we are back in the early Ford manufacturing line, which back then looked like a great advancement and scalable, but that was good for the 1920s.

Taking the unit operations path or a custom device/disposable per process will not enable personalised medicine nor multiple types of therapies to be manufactured efficiently. Therapies like TILs, MILs etc. differ in terms of process income starting material, dose, process steps and reagents. To date, the industry is far from being prepared for commercial manufacturing. The industry is much more focused on the science and by nature are very hesitant in changing the process to fit the needs. This paradigm results in a situation where we all are building hope, developing great therapies and neglecting the manufacturing and cost issues. We all tend to say “this will be solved” but this is a big and complicated task that has to be developed in parallel to the therapy and not after as it will never mature. We need an innovative leap to get the therapies to patients.

What are the supply chain implications when manufacturing at POC?

The supply chain has two sides to the picture with opposite effects. The first is that supplying to a central manufacturing facility is always easier than to several sites that don’t operate as one such as hospitals. Furthermore, quality assurance can be a challenge adding cost and logistics. This can be overcome by central logistic centres, McDonald’s is a logistic company more than a restaurant chain, it has a very big and efficient central logistic arm that works with the branches and ensures supply per demand and quality. To overcome the supply issues, we need to think like McDonald’s as a central logistic and quality solution. This will, down the road, make the manufacturing more efficient, less costly and promises quality.

The other side of the story is the fact that decentralised manufacturing simplifies the most critical, costly and sensitive logistics issue and that is the donor material and end product. If we simplify or eliminate the need to ship the treatment, we improve the quality, efficiency, price and complexity. Therefore, I see this paradigm change as critical and beneficial for the success of autologous cell therapies.  

How does our industry need to work with healthcare professionals to ensure POC manufacturing is possible?

The industry has to see the healthcare as their partners and not customers, you are not selling to the hospital but partnering with them to bring a better cure for the patients. If we see the hospitals as our partners, we can build a system which will enable the needed quality systems and ensure the availability. If we see the hospitals as our customers, we will not be able to build a win-win relationship that shares the product and profit. If we as an industry partner and find the way that PoC manufacturing sites become aligned with us, we will create a paradigm change that will influence healthcare in a whole.

How did ADVA Biotechnology tackle the above issues in the design of Its ADVA X3 solution?

The Adva X3 was designed to enable point of care manufacturing. The device allows process flexibility culturing cells from millions to tens of billions in the same device and kit. The system and kits are designed to do all of the unit operation steps required for the above processes with flexible programming. This means you can do the activation, transduction, expansion, wash and formulate in the same unit tailoring to the process without the need to redesign the kit or the device allowing CAR T, TCR, NK and TILs to be done on the same device. The fact that the system is operated by sensors and controlled with 12 different parameters (such as oxygen, glucose, lactate, pH….), not only allows optimisation but mostly machine learning and reduction of variations by adapting the process to the donor.

Additionally, the device is designed to be closed and simple to operate with remote control options and electronic batch record. The above results in reduced cost of goods, labour and space leading to a scalable model simplifying the manufacturing and logistics. The Adva X3 is designed to do the technology leap that is needed to ensure treatments to patients.

About the interviewee

Dr Karnieli is the founder and CEO of ADVA Biotechnology. A well-known international expert in cell therapy with extensive knowledge of the industry. Dr Karnieli is the founder and President of Atvio Biotech, a leading Innovation centre for cell and gene therapy. Former VP of Technology and Manufacturing at Pluristem Therapeutics and the former VP medical device at Goji solutions. Dr Karnieli served as the chair of several industry committees such as the process and product development committee of the International Society for Cellular Therapies, an expert member in the ISO TC276 Biotechnology standard committee and the former chair of the science and technology committee of the Alliance for Regenerative Medicine. Furthermore, Dr Karnieli serves as an advisor and board member to several of the lead cell therapy in developing companies. Dr Karnieli earned his PhD on Cell and Gene Therapy in the Sackler School of Medicine of Tel Aviv University. He also holds an MBA from the Haifa University business management school.